L2HGDH
Identifiers
Aliases	L2HGDH, C14orf160, L2HGA, L-2-hydroxyglutarate dehydrogenase
External IDs	OMIM: 609584 MGI: 2384968 HomoloGene: 11767 GeneCards: L2HGDH
Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q21.3 Start 50,237,563 bp[1] End 50,312,229 bp[1]
Gene location (Mouse) Chr. Chromosome 12 (mouse)[2] Band 12|12 C2 Start 69,737,207 bp[2] End 69,771,647 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in muscle of leg gastrocnemius muscle kidney islet of Langerhans rectum liver prefrontal cortex ganglionic eminence right lobe of liver secondary oocyte Top expressed in proximal tubule interventricular septum masseter muscle kidney spermatocyte supraoptic nucleus saccule morula left lobe of liver otic placode More reference expression data BioGPS More reference expression data
Gene ontology Molecular function oxidoreductase activity 2-hydroxyglutarate dehydrogenase activity (S)-2-hydroxy-acid oxidase activity Cellular component integral component of membrane mitochondrial inner membrane mitochondrion integral component of mitochondrial inner membrane Biological process 2-oxoglutarate metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 79944 217666 Ensembl ENSG00000087299 ENSMUSG00000020988 UniProt Q9H9P8 Q91YP0 RefSeq (mRNA) NM_024884 NM_145443 RefSeq (protein) NP_079160 NP_663418 Location (UCSC) Chr 14: 50.24 – 50.31 Mb Chr 12: 69.74 – 69.77 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

L-2-hydroxyglutarate dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the L2HGDH gene, also known as C14orf160, on chromosome 14.^[5][6]

Function

This gene encodes L-2-hydroxyglutarate dehydrogenase, a flavin adenine dinucleotide (FAD)-dependent enzyme that oxidizes L-2-hydroxyglutarate to alpha-ketoglutarate in a variety of mammalian tissues. Mutations in this gene cause L-2-hydroxyglutaric aciduria, a rare autosomal recessive neurometabolic disorder resulting in moderate to severe mental retardation.^[6]

L2HGDH codes for a protein that is 50 kDa in size. The L2HGDH protein contains a mitochondrial-targeting transit peptide^[7] and is localized to the mitochondrial inner membrane inside mitochondria inside the cell. The L2HGDH protein catalyzes the following reaction, and requires flavin adenine dinucleotide (FAD) as a co-factor:

(S)-2-hydroxyglutarate + acceptor = 2-oxoglutarate + reduced acceptor.^[5]

L-2-hydroxyglutarate is produced by promiscuous action of malate dehydrogenase on 2-oxoglutarate; the L2HGDH protein is thus an example of a metabolite repair enzyme because it reconverts the useless damage product L-2-hydroxyglutarate back to 2-oxoglutarate.

Clinical significance

Mutations in the L2HGDH gene cause L-2-hydroxyglutaric aciduria, a rare autosomal recessive neurometabolic disorder. Individuals with L2HGDH mutations present toxic accumulation of high concentration of L-2-hydroxyglutaric acid in the plasma and cerebrospinal fluid.^[8] At least 70 disease-causing variants in the L2HGDH gene have been discovered in patients.^[9] Patients with L-2-hydroxyglutaric aciduria are associated with moderate to severe mental retardation, psychomotor retardation, cerebellar ataxia, macrocephaly, or epilepsy.^[9]

L2HGDH has a role in mediating differentiation in T-cells via its activity on S-2HG ^[10]

Molecular interactions

KLK10^[11]